6zrv: Difference between revisions
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==Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-W175F) in Complex with an Inhibitory Nanobody (VHH-s-a93, Nb93)== | |||
<StructureSection load='6zrv' size='340' side='right'caption='[[6zrv]], [[Resolution|resolution]] 1.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6zrv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZRV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6zrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrv OCA], [https://pdbe.org/6zrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zrv RCSB], [https://www.ebi.ac.uk/pdbsum/6zrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrv ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PAs). Apart from being critically involved in fibrinolysis and wound healing, emerging evidence indicates that PAI-1 plays an important role in many diseases, including cardiovascular disease, tissue fibrosis, and cancer. Targeting PAI-1 is therefore a promising therapeutic strategy in PAI-1 related pathologies. Despite ongoing efforts no PAI-1 inhibitors were approved to date for therapeutic use in humans. A better understanding of the molecular mechanisms of PAI-1 inhibition is therefore necessary to guide the rational design of PAI-1 modulators. Here, we present a 1.9 A crystal structure of PAI-1 in complex with an inhibitory nanobody VHH-s-a93 (Nb93). Structural analysis in combination with biochemical characterization reveals that Nb93 directly interferes with PAI-1/PA complex formation and stabilizes the active conformation of the PAI-1 molecule. | |||
Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.,Sillen M, Weeks SD, Strelkov SV, Declerck PJ Int J Mol Sci. 2020 Aug 15;21(16):5859. doi: 10.3390/ijms21165859. PMID:32824134<ref>PMID:32824134</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Declerck | <div class="pdbe-citations 6zrv" style="background-color:#fffaf0;"></div> | ||
[[Category: Sillen | |||
[[Category: Strelkov | ==See Also== | ||
[[Category: Weeks | *[[Plasminogen activator inhibitor|Plasminogen activator inhibitor]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Vicugna pacos]] | |||
[[Category: Declerck PJ]] | |||
[[Category: Sillen M]] | |||
[[Category: Strelkov SV]] | |||
[[Category: Weeks SD]] | |||
Latest revision as of 11:32, 17 October 2024
Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-W175F) in Complex with an Inhibitory Nanobody (VHH-s-a93, Nb93)Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-W175F) in Complex with an Inhibitory Nanobody (VHH-s-a93, Nb93)
Structural highlights
Publication Abstract from PubMedPlasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PAs). Apart from being critically involved in fibrinolysis and wound healing, emerging evidence indicates that PAI-1 plays an important role in many diseases, including cardiovascular disease, tissue fibrosis, and cancer. Targeting PAI-1 is therefore a promising therapeutic strategy in PAI-1 related pathologies. Despite ongoing efforts no PAI-1 inhibitors were approved to date for therapeutic use in humans. A better understanding of the molecular mechanisms of PAI-1 inhibition is therefore necessary to guide the rational design of PAI-1 modulators. Here, we present a 1.9 A crystal structure of PAI-1 in complex with an inhibitory nanobody VHH-s-a93 (Nb93). Structural analysis in combination with biochemical characterization reveals that Nb93 directly interferes with PAI-1/PA complex formation and stabilizes the active conformation of the PAI-1 molecule. Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.,Sillen M, Weeks SD, Strelkov SV, Declerck PJ Int J Mol Sci. 2020 Aug 15;21(16):5859. doi: 10.3390/ijms21165859. PMID:32824134[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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